Abstract

Background

Over the last five years, there have been numerous reports of association of juvenile
idiopathic arthritis with single nucleotide polymorphisms (SNPs) at various loci outside
the major histocompatibility complex (MHC) region. However, the majority of these
association findings have been generated using a limited number of international cohorts,
and thus there is benefit in further independent replication. To address this, we
examined a total of 56 SNPs in 42 non-MHC gene regions previously reported to be associated
with JIA, in the ChiLdhood Arthritis Risk factor Identification sTudY (CLARITY), a
new Australian collection of cases and healthy child controls.

Findings

Genotyping was performed on a total of 324 JIA cases (mean age 9.7 years, 67.3% female)
and 568 controls (mean age 7.8 years, 40.7% female). We demonstrated clear evidence
for replication of association of JIA with SNPs in or around c12orf30, c3orf1, PTPN22, STAT4, and TRAF1-C5, confirming the involvement of these loci in disease risk. Further, we generated evidence
supportive of replication of association of JIA with loci containing AFF3, CD226, MBL2, PSTPIP1, and RANTES (CCL5). These results were robust to sensitivity analyses for ethnicity.

Conclusion

We have provided valuable independent data as to the underlying genetic architecture
of this understudied pediatric autoimmune disease, further confirming five loci outside
the MHC, and supporting a role for a further five loci in determining disease risk.